Prostaglandins are a group of cyclic fatty acids that possess diverse and potent biologic activities affecting cellular function in every organ system. The parent compound, prostanoic acid, contains a 20 carbon chain with a cyclopentane ring. ##STR1## Variations in the number and position of the double bonds and hydroxyl groups determine the physiologic activities of the various prostaglandins.
Conventionally, prostaglandins are divided into types E, F, A, B, C and D based on functions in the cyclopentane ring. Numerical subscripts refer to the number of unsaturations in the side chains-and .alpha. or .beta. subscripts refer to the configuration of the substituents in the ring. The naturally occurring prostaglandins are types E, F, A and B. All naturally occurring prostaglandins have a trans 13,14 position bond and an hydroxyl group at C.sub.15.
The E- and F-type prostaglandins possess an additional hydroxyl at C.sub.11. At C.sub.9, E-type prostaglandins have a carbonyl function while F-type prostaglandins have an hydroxyl. In general, A- and B-type prostaglandins may be regarded as dehydration products of E- type prostaglandins; i.e., the removal of the C.sub.11 hydroxyl and the formation of a double bond in the cyclopentane ring.
The known biologic activities of prostaglandins of the E-type include activities as hypotensive agents, bronchodilators, and gastric acid secretion inhibition agents. [Bergstrom, et al., PHARMACOL. , REV. , 20:1 (1968) ]. However, pharmaceutical use of E-type prostaglandins has been impeded by their instability. E-type prostaglandins generally decompose slowly at room temperature and above, which decomposition is accelerated in the presence of small amounts of acid or base. Accordingly, E-type prostaglandins are unstable in pharmaceutical formulations containing water or hydroxylic compounds. Even in neutral, aqueous solution or in neat state there is a gradual decomposition of E-type prostaglandins to A- and B-type prostaglandins.
Good stability of the E-type prostaglandins has been observed in some solutions and in pure form at temperatures of -20.degree. C. or lower. However, storage at such temperatures is impractical. Some success at stabilization at room temperature has been reported when non-alcoholic compounds such as ethyl acetate and chloroform are employed as solvents for E-type prostaglandins. Such solvents, however, are unsuitable for pharmaceutical dosage applications.
More recently, good stability of E-type prostaglandins was reported with use of triethyl citrate as a solvent (U.S. Pat. No. 4,211,793) and with use of hydroxylated derivatives of fatty acids (U.S. Pat. No. 4,431,833).
Although hair serves no vital function in humans, the psychological impact from excess hair growth or loss of hair can be enormous. For some men in particular, as a result of aging and predisposing genetic factors, scalp baldness occurs in stages often resulting in a complete loss of scalp hair. This baldness is known as male pattern baldness or androgenetic alopecia. It is believed that an accumulation of 5-.alpha.-dihydro testosterone, a tissue-active androgen, in some scalp hair follicles over time causes the regression of hair growth in such follicles. However, androgen production is no higher in men with androgenetic alopecia than in those with full scalps of hair.
There is no effective treatment for androgenetic alopecia at the present time. There have been some reports that minoxidil, a potent vasodilator, has been effective in causing scalp hair growth in patients with androgenetic alopecia. However, contrary to some popular belief, there is no evidence of a vascular deficit to the scalp in patients with androgenetic alopecia.